Causes of Stiff Person Syndrome

From rare diseases.org we see a succinct description of causes of Stiff Person Syndrome:

“
The exact cause of SPS is not known. Some studies in the medical literature indicate that it may be an autoimmune disorder. Autoimmune disorders are caused when the body’s natural defenses (e.g., antibodies) against “foreign” or invading organisms begin to attack healthy tissue for unknown reasons.

Most of those affected have antibodies to glutamic acid decarboxylase (GAD), a protein in inhibitory nerve cells that is involved in the creation (synthesis) of the main inhibitory neurotransmitter called gamma-aminobutyric acid (GABA). GABA helps control muscle movement and prevent hyperexcitibility within the brain and spine. The symptoms of SPS may develop when the immune system mistakenly attacks certain nerve cells (neurons) that produce GAD leading to a deficiency of GABA in the body.

Less commonly, individuals with SPS will have antibodies to amphiphysin, a protein involved in the transmission of signals from one nerve cell to another. In these individuals, breast cancer is quite prevalent.

The exact role that deficiency of GAD plays in the development of SPS is not fully understood. Antibodies to GAD-65 are associated with several other disorders including diabetes. In fact, GAD-65 is the most common antibody produced by people with autoimmune diabetes and many people have these antibodies in that context. In some individuals with SPS no antibodies to GAD are detectable. The cause of SPS in these individuals may ultimately be unknown (idiopathic), but testing for other causes (e.g. amphiphysin antibodies) is usually appropriate. ...”

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